2001
Lack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors
Myung J, Kim K, Lindsten K, Dantuma N, Crews C. Lack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors. Molecular Cell 2001, 7: 411-420. PMID: 11239469, DOI: 10.1016/s1097-2765(01)00188-5.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsBinding SitesCattleCell DivisionCells, CulturedChymotrypsinCysteine EndopeptidasesEndopeptidasesEpoxy CompoundsHumansHydrolysisKetonesKineticsModels, BiologicalMultienzyme ComplexesProtease InhibitorsProteasome Endopeptidase ComplexProtein SubunitsRecombinant Fusion ProteinsSerineSubstrate SpecificityTransfectionConceptsProtein degradation assaysSubunit-specific inhibitorsProtein degradationDegradation assaysCellular proliferationChymotrypsin-like activityPeptidyl-glutamyl peptideEpoxyketone inhibitorsActive siteSuch interactionsInhibitorsAllosteryProteasomeSitesSubunitsInhibitionSubstrateActivityProliferationAssaysPeptidesOccupancy
1999
Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketones
Elofsson M, Splittgerber U, Myung J, Mohan R, Crews C. Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketones. Cell Chemical Biology 1999, 6: 811-822. PMID: 10574782, DOI: 10.1016/s1074-5521(99)80128-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCattleCell DivisionCells, CulturedChymotrypsinCysteine EndopeptidasesCysteine Proteinase InhibitorsDrug DesignEndothelium, VascularEpoxy CompoundsGlutamatesIndicators and ReagentsIrritantsKineticsMacromolecular SubstancesMiceMolecular ConformationMultienzyme ComplexesPeptidesProteasome Endopeptidase ComplexTrypsinConceptsCatalytic activityMolecular probesAcetylated peptidesExcellent selectivityPotent proteasome inhibitorVivo anti-inflammatory activityMost compoundsMajor catalytic activityChymotrypsin-like activityPeptide αAromatic amino acidsEpoxyketonesAminoP2-P4Multicatalytic protease complexPeptidesAnti-inflammatory activitySelectivityProbeLarge multicatalytic protease complexesProteasome inhibitorsAmino acidsSynthesisCompoundsComplexesEpoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity
Meng L, Mohan R, Kwok B, Elofsson M, Sin N, Crews C. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 10403-10408. PMID: 10468620, PMCID: PMC17900, DOI: 10.1073/pnas.96.18.10403.Peer-Reviewed Original ResearchAnimalsAnti-Inflammatory Agents, Non-SteroidalAntibiotics, AntineoplasticCattleCells, CulturedCysteine EndopeptidasesCysteine Proteinase InhibitorsEndothelium, VascularErythrocytesHeLa CellsHumansKineticsMultienzyme ComplexesOligopeptidesProteasome Endopeptidase ComplexTumor Cells, CulturedTumor Suppressor Protein p53UbiquitinsUmbilical VeinsEponemycin exerts its antitumor effect through the inhibition of proteasome function.
Meng L, Kwok BH, Sin N, Crews CM. Eponemycin exerts its antitumor effect through the inhibition of proteasome function. Cancer Research 1999, 59: 2798-801. PMID: 10383134.Peer-Reviewed Original ResearchConceptsProteasome inhibitionCyclin-dependent kinase inhibitorNovel chemotherapeutic strategiesPharmacological interventionsAntitumor effectsPossible cancer therapySubunits LMP2Chemotherapeutic strategiesKinase inhibitorsCellular morphological changesCell cycle progressionCancer therapyCycle progressionInhibitionProteasome functionMorphological changesKey regulatory proteinsProteasomal subunitsTherapy
1998
Eponemycin analogues: syntheses and use as probes of angiogenesis
Sin N, Meng L, Auth H, Crews C. Eponemycin analogues: syntheses and use as probes of angiogenesis. Bioorganic & Medicinal Chemistry 1998, 6: 1209-1217. PMID: 9784862, DOI: 10.1016/s0968-0896(98)00089-3.Peer-Reviewed Original Research
1997
The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2
Sin N, Meng L, Wang M, Wen J, Bornmann W, Crews C. The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 6099-6103. PMID: 9177176, PMCID: PMC21008, DOI: 10.1073/pnas.94.12.6099.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAminopeptidasesAnimalsAntibiotics, AntineoplasticBinding SitesCattleCyclohexanesFatty Acids, UnsaturatedHumansKineticsMammalsMetalloendopeptidasesMethionyl AminopeptidasesMolecular Sequence DataNeovascularization, PathologicO-(Chloroacetylcarbamoyl)fumagillolSaccharomyces cerevisiaeSequence AlignmentSequence Homology, Amino AcidSesquiterpenesConceptsMethionine aminopeptidaseMetAP-1MetAP-2Mammalian proteinsBlood vessel formationVegetative growthTNP-470New blood vessel formationPotent biological activitiesMolecular modeProteinFungal metabolitesVessel formationAnimal model studiesAminopeptidaseAnti-angiogenic compoundsDetailed pharmacological studiesBiological activityImportant targetFumagillinClinical trialsSolid tumorsPharmacological studiesNatural productsSaccharomyces
1996
Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis.
Crews C, Lane W, Schreiber S. Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 4316-4319. PMID: 8633062, PMCID: PMC39533, DOI: 10.1073/pnas.93.9.4316.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBrainCattleConsensus SequenceDepsipeptidesDNA PrimersGTP-Binding ProteinsHumansInfantMolecular Sequence DataMolecular WeightNeuronal Ceroid-LipofuscinosesPeptides, CyclicPolymerase Chain ReactionProtein BindingRatsSequence Homology, Amino AcidThiolester HydrolasesConceptsPalmitoyl-protein thioesteraseInfantile neuronal ceroid lipofuscinosisNeuronal ceroid lipofuscinosisGTP-dependent bindingProgressive loss of brain functionDidemnin BG alpha s subunitProtein synthesis inhibitory activityProteins in vitroCeroid lipofuscinosisSequence similarityPalmitoyl thioesteraseProtein thioesteraseHuman cDNAEF1-alphaS subunitsBrain lysatesH-rasThioesteraseProteinBiological activityLipofuscinosisCDNADidemninInhibitory activity
1994
GTP-dependent binding of the antiproliferative agent didemnin to elongation factor 1 alpha.
Crews CM, Collins JL, Lane WS, Snapper ML, Schreiber SL. GTP-dependent binding of the antiproliferative agent didemnin to elongation factor 1 alpha. Journal Of Biological Chemistry 1994, 269: 15411-15414. PMID: 8195179, DOI: 10.1016/s0021-9258(17)40692-2.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnti-Infective AgentsCarrier ProteinsCattleChromatography, AffinityDepsipeptidesGuanosine TriphosphateHumansIndicators and ReagentsKineticsMolecular Sequence DataPeptide Elongation Factor 1Peptide Elongation FactorsPeptides, CyclicProtein Synthesis InhibitorsSequence Homology, Amino AcidConceptsEF-1 alphaPotential antineoplastic drugElongation factor 1 alphaDidemnin BProtein synthesisAntiproliferative activityG1 cell cycle progressionGTP-dependent bindingFactor 1 alphaClinical trialsCell cycle progressionImmunosuppressive activityAntineoplastic drugsPeptide sequence analysisElongation factorMode of actionUndefined mechanismPresence of GTPGTPase activityCycle progressionNanomolar concentrationsSequence analysisAlphaMarine natural productsIntracellular targets